sb-258585 and Parkinsonian-Disorders

Although the basolateral amygdala (BLA) and serotonin

Topics: Animals; Anti-Anxiety Agents; Anxiety; Basolateral Nuclear Complex; Corpus Striatum; Dopamine; gamma-Aminobutyric Acid; Glutamic Acid; Male; Methylamines; Neural Pathways; Neurons; Norepinephrine; Oxidopamine; Parkinsonian Disorders; Piperazines; Pyridines; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin Agents; Substantia Nigra; Sulfonamides

The role of prelimbic (PrL) 5-HT6 receptors in depression is poorly understood, particularly in Parkinson's disease-related depression. Here we reported that 6-hydroxydopamine lesions in rats decreased sucrose preference and increased immobility time as measured by the sucrose preference and forced swim tests when compared to sham-operated rats, indicating the induction of depressive-like behaviors. Intra-PrL injection of 5-HT6 receptor agonist WAY208466 induced depressive-like responses in sham-operated rats, and produced antidepressant-like effects in the lesioned rats. However, 5-HT6 receptor antagonist SB258585 produced antidepressant-like effects in sham-operated rats, and increased the expression of depressive-like behaviors in the lesioned rats. Neurochemical results showed that intra-PrL injection of WAY208466 and SB258585 decreased or increased dopamine (DA) and noradrenaline (NA) levels in the medial prefrontal cortex, amygdala, habenula and ventral hippocampus in sham-operated and the lesioned rats, respectively. WAY208466 increased the firing rate of PrL glutamate neurons in the two groups of rats, while SB258585 decreased the firing rate of the neurons. Compared to sham-operated rats, the duration of WAY208466 and SB258585 action on the firing rate of glutamate neurons was markedly prolonged in the lesioned rats. The lesion did not change the co-localization of 5-HT6 receptor and glutamate neurons in the PrL. These findings indicate that 5-HT6 receptors in the PrL are involved in the regulation of depressive-like behaviors, which attribute to changes in DA and NA levels in the limbic and limbic-related brain regions. Additionally, the results suggest that the lesion leads to a supersensitization of 5-HT6 receptors on glutamate neurons in the PrL.

Topics: Animals; Depression; Injections, Intraventricular; Male; Methylamines; Oxidopamine; Parkinsonian Disorders; Piperazines; Prefrontal Cortex; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Sulfonamides

Preclinical studies indicate both activation and blockade of serotonin6 (5-HT6) receptors may produce antidepressant-like effects. Depression is a common symptom in Parkinson's disease (PD); however, its pathophysiology is unclear. Here we examined whether 5-HT6 receptors in the dorsal hippocampus (DH) involve in the regulation of PD-associated depression. Unilateral 6-hydroxydopamine lesions of the medial forebrain bundle in rats induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. In sham-operated rats, intra-DH injection of 5HT6 receptor agonist WAY208466 or antagonist SB258585 increased sucrose consumption and decreased immobility time, indicating the induction of antidepressant effects. In the lesioned rats, WAY208466 also produced antidepressant effects, whereas SB258585 decreased sucrose consumption and increased immobility time, indicating the induction of depressive-like behaviors. Neurochemical results showed that WAY208466 did not change dopamine (DA) levels in the medial prefrontal cortex (mPFC), DH and habenula, and noradrenaline (NA) levels in the DH and habenula in sham-operated rats, and SB258585 increased DA and NA levels in these structures. Further, WAY208466 increased DA levels in the mPFC, DH and habenula, and NA level in the habenula in the lesioned rats, and SB258585 decreased DA levels in the mPFC and habenula. Additionally, the lesion did not change the density of neuronal glutamate transporter EAAC1/5-HT6 receptor co-expressing neurons in the DH. Compared to sham-operated rats, these findings suggest that the effects of 5-HT6 receptors in PD-associated depression may be mediated through different neurochemical mechanisms, and the DH is an important site involved in these effects.

Topics: Animals; Antidepressive Agents; Depressive Disorder; Dopamine; Excitatory Amino Acid Transporter 3; Habenula; Hippocampus; Male; Medial Forebrain Bundle; Methylamines; Norepinephrine; Oxidopamine; Parkinsonian Disorders; Piperazines; Prefrontal Cortex; Pyridines; Rats, Wistar; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Sulfonamides